Human monocytes and murine/rat macrophages metabolize modified lipoproteins, such as acetylated LDL, through a specific cell surface receptor. Metabolism of modified lipoproteins produces massive cholesteryl ester deposition as cytoplasmic droplets, giving the cells the appearance of arterial foam cells. Specific aims of the proposal are: (a) to isolate a receptor for abnormal lipoproteins from murine macrophages in quantities sufficient for amino acid and partial sequence analysis (b) to develop polyclonal and monoclonal reagents specific for the murine and human receptor; (c) to isolate cell mutants defective in synthesis and/or function of the receptor. The information and reagents obtained will permit development of probes specific for different regions of the receptor, allow definition of regions of the receptor important for its function, allow identification of the receptor in different cell types and species, allow localization of the receptor in the arterial lesion, and provide information on the synthesis and regulation of the receptor. Foam cell formation is a key event in the development of atheromatous lesions. A receptor for modified lipoproteins may play a role in this foam cell formation in vivo. Combined biochemical and immunochemical data will facilitate evaluation of the receptor's role in atherogenesis and provide information useful in developing reagents to modulate the function of the receptor. In addition to a role in atherogenesis, the receptor may be of importance in regulating macrophage functions such as protease secretion. Biochemical and immunochemical data on the receptor will thus be of importance in further understanding control of macrophage physiology.